Adrenomedullin levels are high in primary aldosteronism due to adenoma and decline after surgical cure.

The aim of the study was to evaluate the possible changes in plasma adrenomedullin (AM) levels in patients with primary aldosteronism before and after surgical resection. The study included 13 patients affected by aldosterone-producing adenoma (9 women, 4 men; mean age 36.2+/-14.2 years) and 20 healthy control subjects (7 women, 13 M; mean age 31.8+/-12.4 years). Unilateral adrenalectomy was performed in all patients and adrenal mass consisted of a benign adrenal cortical adenoma. The mean plasma AM concentrations in patients with primary aldosteronism (36.2+/-19.3 pg/ml) were significantly (p < 0.0001) higher than those of normal subjects (13.2+/-6.2 pg/ml). In these patients the plasma AM levels significantly (p < 0.0001) reduced after surgical removal of the tumours (14.9+/-7.6 pg/ml). In all patients with aldosterone-producing adenoma, tumour diameter correlated with the plasma AM concentrations (r=0.631; p < 0.021). In conclusion, the present investigation shows that in primary aldosteronism due to adrenal adenoma plasma AM levels are higher at the moment of diagnosis and decline after successful adrenal operation.

High plasma endothelin-1 levels in hypertensive patients with low-renin essential hypertension.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide derived from endothelial cells and may be important in the control of systemic blood pressure (BP) and local blood flow. Immunoreactive ET-1 plasma levels may be normal or elevated in human arterial hypertension, although the exact pathophysiological role of ET-1 remains to be established. The aim of our study was to determine the relationship between the components of the renin-angiotensin-aldosterone system and plasma ET-1 levels in patients with low, normal or high-renin essential hypertension. The study groups included 13 patients with low-renin essential hypertension (average age 43.5 +/- 16.2 years), 16 patients with normal-renin essential hypertension (46.5 +/- 13.4 years), 11 patients with high-renin essential hypertension (40.7 +/- 13.8 years) and 12 healthy subjects (43.1 +/- 11.4 years). Our results demonstrated that the mean ET-1 values of all patients with essential hypertension were 10.4 +/- 3.4 pg/ml; there was not a statistical correlation between plasma renin activity (PRA) and the ET-1 levels of hypertensives; instead there was a statistically significant correlation between plasma ET-1 and plasma aldosterone (PA) (r = 0.393; P < 0.026). In particular mean plasma ET-1 values in patients with low-renin essential hypertension (12.6 +/- 2.1 pg/ml) were significantly higher (ANOVA = 0.000, P < 0.05) than those of normotensive subjects (7.7 +/- 1.7 pg/ml), patients with normal-renin essential hypertension (8.5 +/- 2.8 pg/ml), and patients with high-renin essential hypertension (9.9 +/- 3.8 pg/ml), respectively. There was a statistical correlation between PA and ET-1 levels in patients with low-renin essential hypertension (r = 0.619, P < 0.024). Our study demonstrated that there was an increase of circulating ET-1 levels in patients with low-renin essential hypertension and ET-1 plasma levels correlated with PA. The results suggest that ET-1 may play an important role in this particular form of human essential hypertension.

High plasma levels of endothelin-1 in untreated Addison's disease.

The aim of this study has been to investigate the plasma endothelin-1 (ET-1) levels in adult patients with proven Addison's disease (AD). Plasma ET-1 levels were measured in 29 subjects (17 males and 12 females, aged between 20 and 54 years): 15 of them were patients with AD and 14 were sex- and age-matched normal subjects, used as a control group. All patients with AD have been studied under basal conditions and nine of them also after 2 weeks on oral corticosteroid therapy (individual cortisol dosage ranging from 25 to 37.5 mg/day and 0.1 mg/day 9 alpha-fluorohydrocortisone). Extracted plasma ET-1 was determined by a specific radioimmunoassay using rabbit endothelin antisera. Mean ET-1 values in the patients with AD were three times higher than in normal subjects (21.09 +/- 4.38 pg/ml vs 6.72 +/- 1.74 pg/ml; p < 0.0001). Plasma ET-1 levels assayed in the patients with AD after 2 weeks of corticosteroid therapy were significantly decreased (14.47 +/- 3.7 pg/ml vs 22.8 +/- 5.2 pg/ml; -37%; p < 0.001) compared to values in untreated patients. However, the plasma ET-1 values obtained following corticosteroid therapy were still significantly higher (p < 0.001) than those detected in the control subjects. These results clearly indicate that patients with untreated AD have increased circulating ET-1 levels that may be reduced by short-term corticosteroid therapy.

Angiotensin-converting enzyme activity in stools of healthy subjects and patients with celiac disease.

Angiotensin-converting enzyme (ACE) is a dipeptidylcarboxypeptidase that occurs in three types of cells: endothelial, epithelial, and neuroepithelial. ACE activity is present in plasma, urine, and vascular endothelium. High levels of ACE are found in the brush border of human small bowel. The aim of this study was to evaluate ACE activity in human stools and to find a correlation with the intestinal loss of epithelial cells. Fifteen healthy subjects (HS) (8 males, 7 females; age range 6-56 years), 20 patients with celiac disease (CD) (11 males, 9 females; age range 15-53 years), and 18 patients with CD in remission after a gluten-free diet (CD-GFD) (8 males, 10 females; age range 14-54 years) were enrolled in the study. The fecal ACE activity was measured in all groups. Fecal samples were kept at -20 degrees C for a subsequent test. In HS, fecal ACE activity was 21.03 +/- 16.17 nmol/min/100 g (mean +/- SD). In patients with CD with subtotal mucosa atrophy, ACE activity was significantly higher (113 +/- 88.94) than in HS and CD on GFD (36.65 +/- 23.9). We have demonstrated ACE activity in human stools. ACE activity in stools seems to derive from the microvilli of the intestinal mucosa, thus suggesting the potential usefulness of ACE determination as an index of enterocyte damage.

Effects of haemodialysis session on plasma beta-endorphin, ACTH and cortisol in patients with end-stage renal disease.

The effect of a regular haemodialysis session on the plasma concentrations of beta-endorphin, ACTH and cortisol was investigated in 14 patients with end-stage renal disease and 20 healthy controls. Blood for analysis of beta-endorphin, ACTH and cortisol was sampled before and immediately after haemodialysis. In four patients the dialysate was studied for presence of these hormones, but showed no specific activity. The predialysis beta-endorphin, ACTH and cortisol levels did not differ significantly from the control values. The postdialysis levels were significantly higher than the predialysis. Significant linear correlation was found between plasma ACTH and beta-endorphin values in the postdialysis samples. The similarity of plasma beta-endorphin, ACTH and cortisol levels in patients with end-stage renal disease before dialysis and in normal controls indicated integrity of the hypothalamic pituitary-adrenal axis. The significantly increased levels after the dialysis session and the significant correlation between postdialysis plasma beta-endorphin and ACTH suggest that the haemodialysis session was a stressful event.

Plasma endothelin-1 levels in patients with aldosterone-producing adenoma and pheochromocytoma.

The aim of the study was to evaluate possible changes of plasma endothelin-1 levels (ET-1) in patients with hypertension secondary to primary aldosteronism and pheochromocytoma. We enrolled in the study: 12 patients affected by aldosterone-producing adenoma (5 M and 7 W; mean age 42.1 +/- 17.2 years); 8 patients with pheochromocytoma (5 M, 3 W; mean age 36.2 +/- 17.1 years); 15 patients with essential hypertension (9 M, 6 W; mean age 48.5 +/- 10 years). We also enrolled a normal control group (8 M, 12 W; mean age 34.2 +/- 11 years). The mean plasma ET-1 concentrations in patients with pheochromocytoma were significantly higher (23.9 +/- 5.2 pg/ml) than those in normal subjects (7.3 +/- 1.9 pg/ml), in patients with primary aldosteronism (12.1 +/- 3.8 pg/ml) and in patients with essential hypertension (9.2 +/- 3 pg/ml); p < 0.001, respectively. The present investigation demonstrates that in human adrenal hypertension patients with pheochromocytoma have increased circulating ET-1 levels respect to patients with aldosterone-producing adenoma.

Plasma endothelin-1 concentrations in patients with coronary artery disease during stress test before and after nisoldipine administration.

The purpose of this study was to determine the response of plasma levels of endothelin-1 (ET-1) to dynamic exercise in patients with coronary artery disease and chronic stable angina pectoris and positive exercise tolerance test, before and after treatment with the calcium antagonist nisoldipine (20 mg/day buccally for 7 days). Plasma ET-1 levels and hemodynamic parameters (blood pressure and heart rate) were determined at rest, at peak exercise and recovery. All patients had a positive electrically and clinically stress test and all of the eight patients did not developed ECG signs of myocardial ischemia after nisoldipine administration. Before nisoldipine treatment the plasma ET-1 levels did not increase significantly during exercise. After nisoldipine treatment the plasma ET-1 levels were significantly lower at rest and during exercise compared with those revealed before calcium antagonist treatment. In conclusion our results suggest that in patients with chronic stable angina pectoris the treatment with calcium antagonist nisoldipine reduced ischemia and plasma ET-1 levels.

beta-Endorphin and propiomelanocortin-correlates peptides response in suspected and confirmed ischemic heart disease during exercise.

UNLABELLED: In this study, we investigated circulating beta-endorphin, ACTH and cortisol in subjects with suspected coronary artery disease (CAD) and in patients with CAD during stress testing. Group I: 18 subjects, all male (average age 48 +/- 9 yrs) with suspected (CAD) were enrolled. Group II: 35 patients, 30 males and 5 females (average age 54.3 +/- 7 yrs) with CAD, were enrolled. Ten patients had previous myocardial infarction. In all patients that underwent coronarography a stenosis > 75% was found in at least one coronary artery. The stress test was performed with a cycloergometer, increasing work loads 25 watt every 2 min. All subjects and patients were in the recumbent position for at least 30 minutes prior to testing. During this period a 3-way catheter was placed in the antecubital vein and blood was drawn for Beta-endorphin, ACTH and cortisol; additional blood samples were drawn using a pre-chilled syringe at maximum effort and during the recovery period. RESULTS: group I: 9 of the subjects with suspected CAD had either ECG or clinical signs of ischemic during the stress test. In subjects with a negative test, the test was carried out for a longer period of time and at a higher work load. There was an increase in Beta-endorphin and ACTH at peak exercise and during recovery. Plasma cortisol increase during the period of recovery. Group II: 16 of the 35 patients with CAD exhibited ECG signs of induced myocardial ischemia; there was no difference in work loads in patients with positive or negative stress test. Exercise time was reduced in all patients and plasma Beta-endorphin increased at peak exercise and recovery in patients with a negative stress test. In conclusion our study revealed a different response of Beta-endorphin, ACTH and cortisol plasma levels in subjects with suspected CAD and in patients with CAD during exercise testing.

Plasma endothelin-1 levels in normotensive and borderline hypertensive subjects during a standard cold pressor test.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide derived from endothelium. The presence of ET-1 in human vascular endothelium and in the plasma suggests that it may play a role in the regulation of vascular tone and blood pressure (BP) in humans. The aim of this study was to evaluate the behaviour of plasma ET-1 in 10 normotensives (average 36.3 +/- 14.8 years) and 10 borderline hypertensives (average 42.0 +/- 11.7 years) before, during and after a standard cold pressor test. We also evaluated the behaviour of heart rate and BP at the same time. Our results demonstrated that the baseline (-10 and 0 min) plasma ET-1 values were identical for the two groups (8.6 +/- 5.8 and 8 +/- 4.7 pg/ml in normotensives; 7.8 +/- 2.7 and 7 +/- 2.4 pg/ml in borderline hypertensives). A statistically significant increment was verified 10 min after exposure to cold in the borderline hypertensive group (12.1 +/- 5.1 pg/ml) compared with the normotensives group (6.8 +/- 4.5 pg/ml; P < 0.05). In conclusion, our study demonstrated that after 10 min of cold pressor stimulus an increase of circulating ET-1 levels was seen in borderline hypertensives.

Increased plasma levels of endothelin-1 in patients with hyperthyroidism.

Plasma concentrations of endothelin-1 (ET-1) were measured in 25 hyperthyroid subjects, 15 hypothyroid subjects, and 21 age-matched normal controls. In hyperthyroid patients, plasma concentrations of ET-1 were significantly higher than in the control group (P < .0001) and in hypothyroid patients (P < .0001). In contrast, no differences were found between hypothyroid patients and controls. Plasma levels of ET-1 were similarly elevated as in patients with Graves' disease and those with toxic adenoma. No correlations were found between plasma ET-1 levels, thyroid hormones, and thyrotropin (TSH) in hyperthyroid, hypothyroid, and euthyroid groups. The results of our study clearly indicate that in hyperthyroidism, circulating levels of ET-1 are strongly increased, although the pathogenesis of the increase is unclear.

Dynamic exercise induces elevation of plasma levels of endothelin-1 in patients with coronary artery disease.

In this investigation the response of endothelin-1 plasma levels to dynamic exercise in patients with coronary artery disease (CAD) was studied. The study population consisted of 20 patients with CAD, 16 men and 4 women (mean age 53 +/- 8.6 years). Seven normal volunteers all men (mean age 53.4 +/- 4.4 years) were studied as a control group. Seven patients had prior myocardial infarction. All patients and controls exercised on a multi-stage bicycle ergometer; plasma endothelin-1 levels and hemodynamic indices were measured at rest, at peak exercise, and at two and six minutes after exercise. Of the 20 patients examined, 7 (35%) showed electrocardiogrpahic (ECG) signs of myocardial ischemia during the stress test. The mean plasma endothelin-1 concentration increased significantly from 7.8 +/- 3.0 to 13.6 +/- 3.5 pg/mL at exercise peak (P < 0.05) only in patients who did not show ECG signs of myocardial ischemia and returned to baseline values during recovery (six minutes) (9.4 +/- 2.1 pg/mL). In normal subjects baseline endothelin-1 levels (9.4 +/- 4.2 pg/mL) were not significantly altered at peak exercise (10.8 +/- 4.7 pg/mL) and at recovery (11.3 +/- 3.6 pg/mL). The hemodynamic parameters were not correlated with the plasma endothelin-1 levels before, during, and after exercise in all groups. The present study demonstrated that the plasma levels of endothelin-1 in patients with CAD increased significantly during stress testing.

Serum concentrations of osteocalcin in pregnant women with multinodular thyroid goiter undergoing treatment with levothyroxine.

In this study we measured serum osteocalcin (Bone Gla-Protein) to investigate bone metabolism in pregnant women with multinodular thyroid goiter undergoing treatment with levothyroxine (L-T4). Serum concentration of BGP was measured in 18 pregnant women and in 20 non-pregnant women (ages raging from 21-34 years) receiving L-T4 (75-125 micrograms/day). Venous blood samples for RIA determination of serum BGP, plasma thyroid hormone (T3, T4, free T3, free T4) and TSH were collected from the two groups. The samples of the pregnant women group were collected before pregnancy (at the moment the disease was diagnosed without L-T4 therapy) during pregnancy (at the 3rd, 6th and 9th month) and one month after delivery. The normal TSH levels (measured with Irma method) before pregnancy, were significantly reduced during treatment with L-T4 during pregnancy and after delivery (p < 0.005), respectively. Also in the control group TSH levels were reduced during treatment. Serial measurement of serum BGP before pregnancy, (3.4 +/- 1 ng/ml) during pregnancy (3rd: 4.2 +/- 1.5 ng/ml; 6th: 4.2 +/- 1.4 ng/ml; 9th: 2.8 +/- 1.6 ng ml, month respectively) and one month after delivery (3.5 +/- 1.3 ng/ml) did not demonstrate significant variations. Furthermore, in the control group the BGP levels were 3.2 +/- 1.7 ng/ml. There was no correlation between BGP, thyroid hormones and TSH in these groups. These data indicate that the administration of moderate doses of L-T4 in pregnant and in non-pregnant women did not modify the serum BGP levels.

Response of serum angiotensin converting enzyme, plasma renin activity and plasma aldosterone to conventional dialysis in patients on chronic haemodialysis.

The aim of this study was to examine serum angiotensin converting enzyme (SACE) activity and the renin-angiotensin-aldosterone system in patients on chronic haemodialysis during one routine dialysis session. Fourteen patients (8 men and 6 women; mean age 51.9 +/- 17 years) with end stage renal disease, receiving regular haemodialysis treatment for an average of 6 months, were studied. The patients were dialysed for 4 hours three times a week using cellulose membranes (cuprophan). After an overnight fast blood samples were taken from the patients before and after the haemodialysis session. Serum and plasma were separated and stored at -20 degrees C until assayed for SACE, plasma renin activity (PRA) and plasma aldosterone (PA). For comparison, SACE, PRA and PA were also measured in 8 patients after renal allotransplantation and on treatment with cyclosporin A (5 men, 3 women; mean age 38.9 +/- 12.3 years) and in 19 healthy subjects (13 men, 6 women; mean age 38.9 +/- 12.3 years). SACE levels in patients with chronic renal failure and on haemodialysis (17.55 +/- 9.03 nmol/ml/min) and in patients with renal transplantation (18.12 +/- 3.92) were significantly higher than those of the healthy subjects (9.27 +/- 1.67) (p < 0.0001, respectively). At the end of the dialysis session SACE levels in patients with chronic renal failure (14.9 +/- 7.19) did not increase in respect to pre-dialysis levels (17.55 +/- 9.03; p = 0.132). PRA and PA values increased after the dialysis session (p < 0.026 and p < 0.044, respectively). Correlation of SACE with PRA and PA was not demonstrated before or after the dialysis session. In patients with chronic renal failure and on haemodialysis our findings suggest that a disarrangement exists between the circulatory components of the reninangiotensin-aldosterone system before and after the dialysis session.

Serum angiotensin-converting enzyme levels in patients with recent-onset insulin-dependent diabetes after one year of low-dose cyclosporin therapy. IMDIAB Study Group.

Cyclosporin A (CyA) is today used for the treatment of autoimmune diseases and in the past was given also to patients with recent-onset insulin-dependent diabetes mellitus (IDDM). Hypertension is a major hazard in patients receiving CyA. In this study we have evaluated the effect of CyA administered to IDDM patients on blood pressure and serum angiotensin-converting enzyme (SACE), an endopeptidase that is an integral part of the renin-angiotensin and bradykinin systems. Sera from patients affected by recent-onset IDDM who were treated with CyA at the dose of 5 mg/kg body weight in addition to insulin therapy were included in the study (n = 13). Sera from 9 IDDM patients with the same clinical characteristics and followed up for 12 months represented the control group (insulin therapy only). SACE levels were measured at diagnosis and after 12 months. The results showed that SACE levels were elevated in IDDM patients at diagnosis and remained significantly high at 12 months in CyA-treated patients as compared to control patients (P < 0.006). Systolic and diastolic blood pressure were increased at 12 months in CyA-treated patients (p < 0.005 and p < 0.05, respectively). CyA therapy administered even at low doses to IDDM patients may increase SACE levels and also blood pressure. These findings should be considered when CyA is used for therapy of autoimmune diseases.

Reduced serum angiotensin converting enzyme activity in children with congenital hypothyroidism.

In this study levels of serum angiotensin converting enzyme (SACE) were evaluated using colorimetric method in 24 children with congenital hypothyroidism, 28 children from an iodine deficient zone (14 euthyroid, 14 subclinically hypothyroid) and 21 normal children. In the children with congenital hypothyroidism SACE levels (28.15 +/- 6.67 nmol/ml/min) were significantly lower (p < 0.05) than SACE levels in normal children (33.87 +/- 7.00 nmol/ml/min) and in children from an iodine deficient zone (subclinical hypothyroid: 36.05 +/- 7.88 nmol/ml/min or euthyroid: 39.61 +/- 6.83 nmol/ml/min). No statistical difference in SACE levels was revealed in either normal subjects or children from an iodine deficient zone. SACE levels among all the groups were not shown to be different in relation to sex. Average TSH levels, as expected, were significantly higher (p < 0.05) in children with congenital hypothyroidism. The correlation between SACE and TSH levels did not demonstrate a statistical significance in any of the groups studied. In conclusion, our data demonstrated that levels of SACE were significantly reduced in children with congenital hypothyroidism.

Mixed type sweat gland adenoma: a case report.

We describe a case of a young woman with inguinal sweat-gland adenoma, that had histological characteristics of both hidradenoma papilliferum and clear-cell hidradenoma. The neoplastic risk potential for the 2 conditions is discussed.

Amlodipine in ambulatory hypertensive patients: humoral and haemodynamic effects.

In order to evaluate the mid-term effects of amlodipine, a 1,4-dihydropyridine calcium antagonist, as well as its effects on the renin-angiotensin-aldosterone system (RAAS), on water and electrolyte balance, on urinary excretion of albumin (UAE) and on lipid metabolism, thirteen hypertensive patients (2 M, 11 F, mean age 54 years) were studied in the course of 24 weeks of therapy with amlodipine at 5-10 mg/day. Pre-therapy and periodically during therapy, the systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were recorded in the sitting orthostatic positions (2 measurements). Laboratory tests were performed at times O and at 24 wks with the patients fasting for at least 12 h in the recumbent position. The tests included: plasma renin activity (PRA), plasma aldosterone (PA), serum angiotensin converting enzyme (SACE), blood urea nitrogen (BUN), blood creatinine, plasma electrolytes (Na, K, Cl), triglycerides, total cholesterol (TC) and HDL-cholesterol (HDLC), along with 24-h urine samples (with sterile urine) to determine UAE. The results of this study demonstrate that SBP, DBP and HR were significantly reduced during the 24 wks of therapy. The water and electrolyte and renal function were not modified. After treatment the levels of TC were significantly reduced. No change was observed in the RAAS, while the mean levels of UAE were reduced though not significantly. In conclusion, amlodipine was shown to be effective for the therapy of hypertension; it does not cause reflex tachycardia even in mid-term therapy and was effective in reducing TC levels.

[The behavior of serum angiotensin-converting enzyme in normotensive subjects, in subjects with essential hypertension and in subjects with primary hyperaldosteronism on the orthostatic test]. / Il comportamento del serum angiotensin converting enzyme in soggetti normotesi ed in soggetti con ipertensione essenziale ed in soggetti con iperaldosteronismo primario alla prova dell'ortostatismo.

The results of this study demonstrate that only in healthy normotensive subjects during extended orthostatism that the renin-angiotensin-aldosterone system remains integral and is characterized by a significant increase in serum angiotensin-converting enzyme (SACE), plasma renin activity (PRA) and plasma aldosterone (PA). SACE modification do not seems to directly follow that of PRA (as shown by the absence of a direct correlation between SACE and PRA). In essential hypertension, the behavior of SACE seems to change, without demonstrating a significant increase in the mean levels of this enzyme. Finally in hypertension of known origin, such as primary hyperaldosteronism, the low levels of SACE in the recumbent position (not stimulated by orthostatism) seem to depend (by mechanism of negative biofeedback) on the increased serum levels of PA, which is moreover verified in the same group for PRA.